Variant chr5-103151384-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001276277.3(PPIP5K2):c.1028+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,583,028 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 27 hom. )

Consequence

PPIP5K2
NM_001276277.3 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.43

Variant links:

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

PPIP5K2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-103151384-T-G is Benign according to our data. Variant chr5-103151384-T-G is described in ClinVar as [Benign]. Clinvar id is 3038048.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1867/152248) while in subpopulation AFR AF= 0.0435 (1807/41558). AF 95% confidence interval is 0.0418. There are 35 homozygotes in gnomad4. There are 892 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIP5K2	NM_001276277.3 linkuse as main transcript	c.1028+10T>G		intron_variant		ENST00000358359.8	NP_001263206.1	O43314-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIP5K2	ENST00000358359.8 linkuse as main transcript	c.1028+10T>G		intron_variant		1	NM_001276277.3	ENSP00000351126.3		O43314-1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1858

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00303

AC:

708

AN:

233354

Hom.:

AF XY:

0.00208

AC XY:

264

AN XY:

126676

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000753

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000644

Gnomad OTH exome

AF:

0.000716

GnomAD4 exome

AF:

0.00121

AC:

1731

AN:

1430780

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

753

AN XY:

712444

show subpopulations

Gnomad4 AFR exome

AF:

0.0438

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000195

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.0123

AC:

1867

AN:

152248

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

892

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00579

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00318

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPIP5K2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over